Could lncRNAs contribute to β-cell identity and its loss in Type 2 diabetes?

2013 ◽  
Vol 41 (3) ◽  
pp. 797-801 ◽  
Author(s):  
Timothy J. Pullen ◽  
Guy A. Rutter
Keyword(s):  
Type 2 Diabetes ◽  
Cell Mass ◽  
Cell Types ◽  
Human Populations ◽  
Β Cell ◽  
Cell Identity ◽  
Genome Wide ◽  
And Function

The progression of Type 2 diabetes is accompanied by diminishing islet β-cell mass and function. It has been proposed that β-cells are lost not only through apoptosis, but also by dedifferentiating into progenitor-like cells. There is therefore much interest in the mechanisms which define and maintain β-cell identity. The advent of genome-wide analyses of chromatin modifications has highlighted the role of epigenetic factors in determining cell identity. There is also evidence from both human populations and animal models for an epigenetic component in susceptibility to Type 2 diabetes. The mechanisms responsible for defining the epigenetic landscape in individual cell types are poorly understood, but there is growing evidence of a role for lncRNAs (long non-coding RNAs) in this process. In the present paper, we discuss some of the mechanisms through which lncRNAs may contribute to β-cell identity and Type 2 diabetes risk.

scholarly journals Pancreatic β-Cell Proliferation in Obesity1,2

2014 ◽  
Vol 5 (3) ◽  
pp. 278-288 ◽  
Author(s):  
Amelia K. Linnemann ◽  
Mieke Baan ◽  
Dawn Belt Davis
Keyword(s):  
Type 2 Diabetes ◽  
Cell Proliferation ◽  
Cell Mass ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Extracellular Signals ◽  
Secreted Factors ◽  
And Function ◽  
Hepatocyte Growth

Abstract Because obesity rates have increased dramatically over the past 3 decades, type 2 diabetes has become increasingly prevalent as well. Type 2 diabetes is associated with decreased pancreatic β-cell mass and function, resulting in inadequate insulin production. Conversely, in nondiabetic obesity, an expansion in β-cell mass occurs to provide sufficient insulin and to prevent hyperglycemia. This expansion is at least in part due to β-cell proliferation. This review focuses on the mechanisms regulating obesity-induced β-cell proliferation in humans and mice. Many factors have potential roles in the regulation of obesity-driven β-cell proliferation, including nutrients, insulin, incretins, hepatocyte growth factor, and recently identified liver-derived secreted factors. Much is still unknown about the regulation of β-cell replication, especially in humans. The extracellular signals that activate proliferative pathways in obesity, the relative importance of each of these pathways, and the extent of cross-talk between these pathways are important areas of future study.

scholarly journals Clinical Potential of Extracellular Vesicles in Type 2 Diabetes

2021 ◽  
Vol 11 ◽  
Author(s):  
Jie Liu ◽  
Xin Sun ◽  
Fu-Liang Zhang ◽  
Hang Jin ◽  
Xiu-Li Yan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Extracellular Vesicles ◽  
Sedentary Lifestyle ◽  
Cell Mass ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Peripheral Tissues ◽  
And Function ◽  
Clinical Potential

Type 2 diabetes (T2D) is a major public health disease which is increased in incidence and prevalence throughout the whole world. Insulin resistance (IR) in peripheral tissues and insufficient pancreatic β-cell mass and function have been recognized as primary mechanisms in the pathogenesis of T2D, while recently, systemic chronic inflammation resulting from obesity and a sedentary lifestyle has also gained considerable attention in T2D progression. Nowadays, accumulating evidence has revealed extracellular vesicles (EVs) as critical mediators promoting the pathogenesis of T2D. They can also be used in the diagnosis and treatment of T2D and its complications. In this review, we briefly introduce the basic concepts of EVs and their potential roles in the pathogenesis of T2D. Then, we discuss their diagnostic and therapeutic potentials in T2D and its complications, hoping to open new prospects for the management of T2D.

scholarly journals Cell-Free DNA Fragments as Biomarkers of Islet β-Cell Death in Obesity and Type 2 Diabetes

2021 ◽  
Vol 22 (4) ◽  
pp. 2151
Author(s):  
Marilyn Arosemena ◽  
Farah A. Meah ◽  
Kieren J. Mather ◽  
Sarah A. Tersey ◽  
Raghavendra G. Mirmira
Keyword(s):  
Type 2 Diabetes ◽  
Cell Death ◽  
Cell Mass ◽  
Dna Fragments ◽  
Β Cell ◽  
Modified Dna ◽  
Function Loss ◽  
And Function ◽  
Study Designs

Type 2 diabetes (T2D) typically occurs in the setting of obesity and insulin resistance, where hyperglycemia is associated with decreased pancreatic β-cell mass and function. Loss of β-cell mass has variably been attributed to β-cell dedifferentiation and/or death. In recent years, it has been proposed that circulating epigenetically modified DNA fragments arising from β cells might be able to report on the potential occurrence of β-cell death in diabetes. Here, we review published literature of DNA-based β-cell death biomarkers that have been evaluated in human cohorts of islet transplantation, type 1 diabetes, and obesity and type 2 diabetes. In addition, we provide new data on the applicability of one of these biomarkers (cell free unmethylated INS DNA) in adult cohorts across a spectrum from obesity to T2D, in which no significant differences were observed, and compare these findings to those previously published in youth cohorts where differences were observed. Our analysis of the literature and our own data suggest that β-cell death may occur in subsets of individuals with obesity and T2D, however a more sensitive method or refined study designs are needed to provide better alignment of sampling with disease progression events.

scholarly journals Genistein ameliorates hyperglycemia in a mouse model of nongenetic type 2 diabetes

2012 ◽  
Vol 37 (3) ◽  
pp. 480-488 ◽  
Author(s):  
Zhuo Fu ◽  
Elizabeth R. Gilbert ◽  
Liliane Pfeiffer ◽  
Yanling Zhang ◽  
Yu Fu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glycemic Control ◽  
Mouse Model ◽  
Dietary Intake ◽  
Cell Mass ◽  
Diabetic Mice ◽  
Β Cell ◽  
And Function

While peripheral insulin resistance is common during obesity and aging in mice and people, the progression to type 2 diabetes (T2D) is largely due to loss of β-cell mass and function through apoptosis. We recently reported that genistein, a soy derived isoflavone, can improve glycemic control and β-cell function in insulin-deficient diabetic mice. However, whether it can prevent β-cell loss and diabetes in T2D mice is unknown. Our current study aimed to investigate the effect of dietary supplemented genistein in a nongenetic T2D mouse model. Nongenetic, middle-aged obese diabetic mice were generated by high fat diet and a low dose of streptozotocin injection. The effect of dietary supplementation of genistein on glycemic control and β-cell mass and function was determined. Dietary intake of genistein (250 mg·kg–1 diet) improved hyperglycemia, glucose tolerance, and blood insulin level in obese diabetic mice, whereas it did not affect body weight gain, food intake, fat deposit, plasma lipid profile, and peripheral insulin sensitivity. Genistein increased the number of insulin-positive β-cell in islets, promoted islet β-cell survival, and preserved islet mass. In conclusion, dietary intake of genistein could prevent T2D via a direct protective action on β-cells without alteration of periphery insulin sensitivity.

Long noncoding RNAs as novel biomarkers for Type 2 diabetes

2020 ◽  
Vol 14 (15) ◽  
pp. 1501-1511
Author(s):  
Han Zhu ◽  
Xiaolan Bian ◽  
Jingru Gong ◽  
Ping Yu ◽  
Huiping Lu
Keyword(s):  
Type 2 Diabetes ◽  
Cell Mass ◽  
Noncoding Rnas ◽  
Glucagon Secretion ◽  
Long Noncoding Rnas ◽  
Β Cell ◽  
Metabolic Markers ◽  
Novel Biomarkers ◽  
And Function

Type 2 diabetes (T2D) is a metabolic disease characterized by disordered glucagon secretion, insulin resistance in target tissues, and decreased islet β-cell mass and function. The routine diagnosis was based on measurements of metabolic markers, while genetic risk factors have been considered to increase the probability of predicting the development of the disease. Recent evidence suggests that long noncoding RNAs (lncRNAs) regulate gene expression in various physiological and pathological processes. As increasing lncRNAs are identified in β cells, understanding the regulatory roles of lncRNAs in T2D becomes indispensable. In this review, we discuss the potential role of lncRNAs contributing to β-cell identity and T2D susceptibility, which provide a perspective insight into the development of novel diagnosis biomarkers for T2D.

scholarly journals m6A mRNA Methylation Controls Functional Maturation in Neonatal Murine β Cells

2020 ◽  
Author(s):  
Ada Admin ◽  
Yanqiu Wang ◽  
Jiajun Sun ◽  
Zhen Lin ◽  
Weizhen Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Mass ◽  
Rna Modification ◽  
Β Cells ◽  
Β Cell ◽  
Functional Maturation ◽  
Mass Expansion ◽  
Endocrine Progenitors

<a>m<sup>6</sup>A RNA modification is essential during embryonic development of various organs; however, its role in embryonic and early postnatal islet development remains unknown.</a><a></a><a> </a>Mice in which RNA methyltransferase-like 3/14 (Mettl3/14) were deleted in Ngn3<sup>+</sup> endocrine progenitors (<i>Mettl3/14<sup>nKO</sup></i>) developed hyperglycemia and hypo-insulinemia at 2 weeks after birth. <a></a><a>We found that Mettl3/14 specifically regulated both functional maturation and mass expansion of neonatal</a><a></a><a> β cell</a>s before weaning. Transcriptome and m<sup>6</sup>A methylome analyses provided m<sup>6</sup>A-dependent mechanisms in regulating<a> cell</a> identity, insulin secretion and proliferation in neonatal<a></a><a> </a><a></a><a>β</a> cells.<a></a><a> Importantly, we found that Mettl3/14 were dispensable for β cell differentiation, but directly regulated essential transcriptional factor MafA expression</a><a> at least partially via modulating its mRNA stability and failure to maintain this modification impacted the ability to fulfill β cell functional maturity. </a>In both diabetic <i>db/db</i> mice and type 2 diabetes patients, decreased Mettl3/14 expression in <a></a><a>β</a> cells were observed, suggesting its possible role in type 2 diabetes. Our stud­­­­­­<sub>­­­</sub>y unraveled the essential role of Mettl3/14 in neonatal β cell development and functional maturation, both of which determined functional β cell mass and glycemic control in adulthood.<b></b>

scholarly journals m6A mRNA Methylation Controls Functional Maturation in Neonatal Murine β Cells

2020 ◽  
Author(s):  
Ada Admin ◽  
Yanqiu Wang ◽  
Jiajun Sun ◽  
Zhen Lin ◽  
Weizhen Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Mass ◽  
Rna Modification ◽  
Β Cells ◽  
Β Cell ◽  
Functional Maturation ◽  
Mass Expansion ◽  
Endocrine Progenitors

<a>m<sup>6</sup>A RNA modification is essential during embryonic development of various organs; however, its role in embryonic and early postnatal islet development remains unknown.</a><a></a><a> </a>Mice in which RNA methyltransferase-like 3/14 (Mettl3/14) were deleted in Ngn3<sup>+</sup> endocrine progenitors (<i>Mettl3/14<sup>nKO</sup></i>) developed hyperglycemia and hypo-insulinemia at 2 weeks after birth. <a></a><a>We found that Mettl3/14 specifically regulated both functional maturation and mass expansion of neonatal</a><a></a><a> β cell</a>s before weaning. Transcriptome and m<sup>6</sup>A methylome analyses provided m<sup>6</sup>A-dependent mechanisms in regulating<a> cell</a> identity, insulin secretion and proliferation in neonatal<a></a><a> </a><a></a><a>β</a> cells.<a></a><a> Importantly, we found that Mettl3/14 were dispensable for β cell differentiation, but directly regulated essential transcriptional factor MafA expression</a><a> at least partially via modulating its mRNA stability and failure to maintain this modification impacted the ability to fulfill β cell functional maturity. </a>In both diabetic <i>db/db</i> mice and type 2 diabetes patients, decreased Mettl3/14 expression in <a></a><a>β</a> cells were observed, suggesting its possible role in type 2 diabetes. Our stud­­­­­­<sub>­­­</sub>y unraveled the essential role of Mettl3/14 in neonatal β cell development and functional maturation, both of which determined functional β cell mass and glycemic control in adulthood.<b></b>

Sign in / Sign up

Export Citation Format

Share Document